Biomedical subjects

John Kirk

Publications and source records attributed to John Kirk.

12 recordsLinked to original sources

PubMed2006

Absence of aquaporin-4 expression in lesions of neuromyelitis optica but increased expression in multiple sclerosis lesions and normal-appearing white matter.

Aquaporin-4 (AQP4) has recently been implicated in the pathogenesis of neuromyelitis optica (NMO) where it has been identified as the first defined autoantigen pertinent to an inflammatory demyelinating disorder of the human CNS. Furthermore, a recent case report has shown a lack of AQP4 expression in the spinal cord lesions of NMO. However, the pattern of AQP4 expression in multiple sclerosis (MS) tissues has not been well-defined. In the present investigation we have confirmed a lack of expression of AQP4 in optic and spinal cord lesions in NMO which contrasted sharply with the increased levels of AQP4 expression seen in MS lesions. Furthermore a detailed immunohistochemical and semi-quantitative analysis is used to describe the expression pattern of AQP4 on well-characterized tissue microarray samples of MS and control white matter. Anatomically AQP4 was more highly expressed in all categories of MS tissue compared to normal control tissues with the most abundant expression in active lesions. Within active lesions AQP4 expression was significantly correlated with expression of the pro-inflammatory cytokine osteopontin. At the cellular level dual-labeling immunofluoresence demonstrated that increased expression of AQP4 was most pronounced at the astrocytic endfeet but was also associated with the cell bodies of astrocytes in the tissue parenchyma. The finding of increased AQP4 expression in MS lesions in contrast to the lack of expression in NMO lesions may suggest different mechanisms of initiation and progression between the two disease states.

Aquaporin 4↗

PubMed2006

Differences in expression of junctional adhesion molecule-A and beta-catenin in multiple sclerosis brain tissue: increasing evidence for the role of tight junction pathology.

Previously we have employed antibodies to the tight junction (TJ)-associated proteins ZO-1 and occludin to describe endothelial tight junction abnormalities, in lesional and normal appearing white matter, in primary and secondary progressive multiple sclerosis (MS). This work is extended here by use of antibodies to the independent TJ-specific proteins and junctional adhesion molecule A & B (JAM-A, JAM-B). We have also assessed the expression in MS of beta-catenin, a protein specific to the TJ-associated adherens junction. Immunocytochemistry and semiquantitative confocal microscopy for JAM-A and beta-catenin was performed on snap-frozen sections from MS cases (n=11) and controls (n=6). Data on 1,443 blood vessels was acquired from active lesions (n=13), inactive lesions (n=13), NAWM (n=20) and control white matter (n=13). In MS abnormal JAM-A expression was found in active (46%) and inactive lesions (21%), comparable to previous data using ZO-1. However, a lower level of TJ abnormality was found in MS NAWM using JAM-A (3%) compared to ZO-1 (13%). JAM-B was strongly expressed on a small number of large blood vessels in control and MS tissues but at too low a level for quantitative analysis. By comparison with the high levels of abnormality observed with the TJ proteins, the adherens junction protein beta-catenin was normally expressed in all MS and control tissue categories. These results confirm, by use of the independent marker JAM-A, that TJ abnormalities are most frequent in active white matter lesions. Altered expression of JAM-A, in addition to affecting junctional tightness may also both reflect and affect leukocyte trafficking, with implications for immune status within the diseased CNS. Conversely, the adherens junction component of the TJ, as indicated by beta-catenin expression is normally expressed in all MS and control tissue categories.

Brain↗

PubMed2006

Observations on intrauterine oxygen tension measured by fibre-optic microsensors.

Understanding the biology of reproductive organs is essential for the development of assisted reproductive techniques. There is at present no direct evidence for either the concentration and dynamics of intrauterine oxygen tension at the endometrial surface, nor its importance for the receptiveness of the endometrium. In this study a new method measured mid-cycle (ranging from day 12-18) endometrial surface oxygen tension in 21 patients referred to intrauterine insemination (IUI). Time series was measured online for a period of 5-10 min. The (mean) individual oxygen tension among patients varied from 4 to 27% air saturation. Overall mean oxygen tension among all patients was 11.8% air saturation. Within the same patient, considerable time-related variations were observed. Some patients exhibited rhythmic oscillations with a frequency in the order of 1 min, whereas others did not show any regular patterns. A good description of endometrial surface oxygen concentration and dynamics was thus obtained, but given the relatively small number of participants, an association with pregnancy following insemination could not be established. Further studies using this new method could elucidate the association between individual intrauterine activity, embryo implantation and endometrial surface oxygen tension.

Adult↗

PubMed2006

The PediaFlow pediatric ventricular assist device.

The very limited options available to treat ventricular failure in patients with congenital and acquired heart diseases have motivated the development of a pediatric ventricular assist device (VAD). Our effort involves a consortium consisting of the University of Pittsburgh, Carnegie Mellon University, Children's Hospital of Pittsburgh, World Heart Corporation, and LaunchPoint Technologies, LLC. The overall aim of our program is to develop a highly reliable, biocompatible VAD for chronic support (6 months) of the unique and high-risk population of children between 3 kg and 15 kg (patients from birth to 2 years of age). The innovative pediatric VAD we are developing (PediaFlow) is based on a miniature mixed-flow turbodynamic pump featuring magnetic levitation, with the design goal being to assure minimal blood trauma and risk of thrombosis. This article discusses the limitations of current pediatric cardiac assist treatment options and the work to date by our consortium toward the development of a pediatric VAD.

Biocompatible Materials↗

PubMed2006

HeartQuest ventricular assist device magnetically levitated centrifugal blood pump.

Improvements in implantable ventricular assist device (VAD) performance will be required to obtain patient outcomes that are comparable with those of heart transplantation. The HeartQuest VAD (WorldHeart, Oakland, CA, U.S.A.) is an advanced device, with full magnetic suspension of the rotor, designed to address specific clinical shortcomings in existing devices and to maximize margins of safety and performance for an implantable assist device. The device dimensions are 35 x 75 mm, with a total weight of 440 g. The system was designed using extensive computer modeling of device function; a total of two iterations of device prototypes were built before building the clinical version. Animal study results have been very promising, with over 30 calf studies completed. Plasma-free hemoglobin levels returned to preoperative levels, and other hematology results were in the normal ranges. Highlights include clean surfaces seen in a 116-day experiment with no anticoagulation after day 43. Feasibility clinical trials are planned to start in 2006.

Animals↗

PubMed2006

Towards the development of a pediatric ventricular assist device.

The very limited options available to treat ventricular failure in children with congenital and acquired heart diseases have motivated the development of a pediatric ventricular assist device at the University of Pittsburgh (UoP) and University of Pittsburgh Medical Center (UPMC). Our effort involves a consortium consisting of UoP, Children's Hospital of Pittsburgh (CHP), Carnegie Mellon University, World Heart Corporation, and LaunchPoint Technologies, Inc. The overall aim of our program is to develop a highly reliable, biocompatible ventricular assist device (VAD) for chronic support (6 months) of the unique and high-risk population of children between 3 and 15 kg (patients from birth to 2 years of age). The innovative pediatric ventricular assist device we are developing is based on a miniature mixed flow turbodynamic pump featuring magnetic levitation, to assure minimal blood trauma and risk of thrombosis. This review article discusses the limitations of current pediatric cardiac assist treatment options and the work to date by our consortium toward the development of a pediatric VAD.

Biocompatible Materials↗

PubMed2004

Women's load carriage performance using modular lightweight load-carrying equipment.

The purposes of this study were to evaluate how Modular Lightweight Load-Carrying Equipment (MOLLE) fits women while walking on level surfaces with different loads, to examine women's load carriage performance before and after a simulated march using five load levels, and to examine the relationship between shoulder and leg muscle strength and load carriage performance of women while carrying loads using MOLLE. Seven physically active women carried five levels of load (no load, 20, 30, 40, and 50 pounds) using MOLLE. With increased loads, women showed increased double-limb support time, decreased single-limb support time, increased trunk forward inclination excursion, decreased knee excursion, decreased medial-lateral excursion of center of gravity (COG), and increased vertical excursion of COG. Hip abductor strength was a strong predictor of COG vertical excursion. Some women required modification of the padded hip belt to ensure weight distributed evenly around the pelvis.

Adolescent↗

PubMed2004

Bioterrorism: development of large-scale medical readiness using multipoint distance-based simulation training.

Accordingly to HIRSA, 35,000 health professionals need to be trained in recognition and acute field treatment of victims of bioterrorism within year 2004 alone The Department of Defense anticipates even larger numbers. Training of very large number of healthcare workers is particularly daunting in the context of "just-in-time" education. The paper presents utilization of simulation-based distance training as a particularly useful tool in rapid development of readiness in a large population of widely distributed medical and lay personnel facing imminent threat of a chem/bioterrorism incident.

Adult↗

PubMed2003

Tight junctional abnormality in multiple sclerosis white matter affects all calibres of vessel and is associated with blood-brain barrier leakage and active demyelination.

Blood-brain barrier (BBB) hyperpermeability in multiple sclerosis (MS) is associated with lesion pathogenesis and has been linked to pathology in microvascular tight junctions (TJs). This study quantifies the uneven distribution of TJ pathology and its association with BBB leakage. Frozen sections from plaque and normal-appearing white matter (NAWM) in 14 cases were studied together with white matter from six neurological and five normal controls. Using single and double immunofluorescence and confocal microscopy, the TJ-associated protein zonula occludens-1 (ZO-1) was examined across lesion types and tissue categories, and in relation to fibrinogen leakage. Confocal image data sets were analysed for 2198 MS and 1062 control vessels. Significant differences in the incidence of TJ abnormalities were detected between the different lesion types in MS and between MS and control white matter. These were frequent in oil-red O (ORO)(+) active plaques, affecting 42% of vessel segments, but less frequent in ORO(-) inactive plaques (23%), NAWM (13%), and normal (3.7%) and neurological controls (8%). A similar pattern was found irrespective of the vessel size, supporting a causal role for diffusible inflammatory mediators. In both NAWM and inactive lesions, dual labelling showed that vessels with the most TJ abnormality also showed most fibrinogen leakage. This was even more pronounced in active lesions, where 41% of vessels in the highest grade for TJ alteration showed severe leakage. It is concluded that disruption of TJs in MS, affecting both paracellular and transcellular paths, contributes to BBB leakage. TJ abnormality and BBB leakage in inactive lesions suggests either failure of TJ repair or a continuing pathological process. In NAWM, it suggests either pre-lesional change or secondary damage. Clinically inapparent TJ pathology has prognostic implications and should be considered when planning disease-modifying therapy.

Adolescent↗

PubMed2002

Prevalence of and risk factors for Salmonella in water offered to weaned dairy calves in California, USA.

Water from troughs used by weaned dairy calves was sampled on California, USA dairies to determine the prevalence and associated risk factors for Salmonella contamination. Salmonella were found on 4 of 48 dairies (4/82 water samples) in fall 1998 and on 8 of the same 37 dairies (8/83 water samples) in summer, 1999. Serotypes isolated from the water were Salmonella meleagridis and Salmonella typhimurium. Primary risk factors associated with the increased prevalence of Salmonella in water offered to weaned dairy calves were a continuous water tank-filling method compared to a valve (an "on-demand" procedure) and a water pH>8.

Animals↗

PubMed2002

Rhabdomyomatous mesenchymal hamartoma: an unusual dermal entity with a report of two cases and a review of the literature.

BACKGROUND: Rhabdomyomatous mesenchymal hamartoma (RMH) is a rare congenital lesion of the dermis and soft tissues consisting of a disordered and varied collection of mature adipose tissue, skeletal muscle, adnexal elements and nerve bundles. This entity exists under various names including striated muscle hamartoma, congenital midline hamartoma, and hamartoma of cutaneous adnexa and mesenchyme. Several published cases report the occurrence of RMH within the setting of other uncommon congenital abnormalities. METHODS: We report the clinical and pathologic features of two cases of rhabdomyomatous mesenchymal hamartoma. Patient 1 is a 71-year-old man who presented for removal of a nodule located on his temple that had been traumatized during a recent haircut. Patient 2 is a 4-month-old infant with amnion rupture sequence and rare craniofacial abnormalities including facial clefts, microphthalmia, bilateral colobomas, and a mobile fingerlike projection above the left medial canthus. RESULTS: Histological examination in both cases showed a deep dermal and subcutaneous fat collection of disorganized skeletal muscle fibers, adipose and neural tissue, and adnexal structures. Characteristically, the skeletal muscle approximated folliculosebaceous structures in a haphazard manner. CONCLUSIONS: RMH is a rare benign condition of the deep dermis and subcutaneous fat with only 22 cases existing in the English literature. To our knowledge, this is the first report of an elderly man presenting with RMH, presumptively present since birth. There was no evidence of cellular or malignant degeneration. While the etiology of RMH is unknown, possible explanations include aberrancy in the embryonic migration of mesodermally derived tissues or a genetic defect predisposing to the formation of hamartomas.

Abnormalities, Multiple↗

PubMed2002

Abnormal endothelial tight junctions in active lesions and normal-appearing white matter in multiple sclerosis.

Blood-brain barrier (BBB) breakdown, demonstrable in vivo by enhanced MRI is characteristic of new and expanding inflammatory lesions in relapsing-remitting and chronic progressive multiple sclerosis (MS). Subtle leakage may also occur in primary progressive MS. However, the anatomical route(s) of BBB leakage have not been demonstrated. We investigated the possible involvement of interendothelial tight junctions (TJ) by examining the expression of TJ proteins (occludin and ZO-1 ) in blood vessels in active MS lesions from 8 cases of MS and in normal-appearing white (NAWM) matter from 6 cases. Blood vessels (10-50 per frozen section) were scanned using confocal laser scanning microscopy to acquire datasets for analysis. TJ abnormalities manifested as beading, interruption, absence or diffuse cytoplasmic localization of fluorescence, or separation of junctions (putative opening) were frequent (affecting 40% of vessels) in oil-red-O-positive active plaques but less frequent in NAWM (15%), and in normal (< 2%) and neurological controls (6%). Putatively "open" junctions were seen in vessels in active lesions and in microscopically inflamed vessels in NAWM. Dual fluorescence revealed abnormal TJs in vessels with pre-mortem serum protein leakage. Abnormal or open TJs, associated with inflammation may contribute to BBB leakage in enhancing MRI lesions and may also be involved in subtle leakage in non-enhancing focal and diffuse lesions in NAWM. BBB disruption due to tight junctional pathology should be regarded as a significant form of tissue injury in MS, alongside demyelination and axonopathy.

Adolescent↗